Two model systems, rats of various ages and human diploid cell lines (WI-38), will be used in this project to study three age-related events: (1) the shutting down of cellular proliferation during aging, (2) the structure-function modification as a result of nuclear-cytoplasmic interaction, (3) the effect of genomeric variations on life span. The aging process in rats represents an example of a normal, interacting developmental event, while the human diploid cell line symbolizes a distinctive cellular aging in vitro. Two systems, although different in many respects, are complementary approaches. Our findings on the WI-38 cell line system will be useful in pinpointing key events to look for in the normal aging processes in individual organisms such as the aging rats. The knowledge we gain from these studies shall, in turn, contribute to our understanding in human aging.